Dataset Information

Hispidulin Attenuates Cardiac Hypertrophy by Improving Mitochondrial Dysfunction.

ABSTRACT: Cardiac hypertrophy is a pathophysiological response to harmful stimuli. The continued presence of cardiac hypertrophy will ultimately develop into heart failure. The mitochondrion is the primary organelle of energy production, and its dysfunction plays a crucial role in the progressive development of heart failure from cardiac hypertrophy. Hispidulin, a natural flavonoid, has been substantiated to improve energy metabolism and inhibit oxidative stress. However, how hispidulin regulates cardiac hypertrophy and its underlying mechanism remains unknown. We found that hispidulin significantly inhibited pressure overload-induced cardiac hypertrophy and improved cardiac function in vivo and blocked phenylephrine (PE)-induced cardiomyocyte hypertrophy in vitro. We further proved that hispidulin remarkably improved mitochondrial function, manifested by increased electron transport chain (ETC) subunits expression, elevated ATP production, increased oxygen consumption rates (OCR), normalized mitochondrial morphology, and reduced oxidative stress. Furthermore, we discovered that Sirt1, a well-recognized regulator of mitochondrial function, might be a target of hispidulin, as evidenced by its upregulation after hispidulin treatment. Cotreatment with EX527 (a Sirt1-specific inhibitor) and hispidulin nearly completely abolished the antihypertrophic and protective effects of hispidulin on mitochondrial function, providing further evidence that Sirt1 could be the pivotal downstream effector of hispidulin in regulating cardiac hypertrophy.

SUBMITTER: Wang Y

PROVIDER: S-EPMC7726192 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Hispidulin Attenuates Cardiac Hypertrophy by Improving Mitochondrial Dysfunction.

Wang Yan Y Xie Zengshuo Z Jiang Nan N Wu Zexuan Z Xue Ruicong R Dong Bin B Fan Wendong W Dai Gang G Chen Chen C Li Jiayong J Chen Hao H Ye Zi Z Fang Rong R Choy Manting M Zhao Jingjing J Dong Yugang Y Liu Chen C

Frontiers in cardiovascular medicine 20201126

Cardiac hypertrophy is a pathophysiological response to harmful stimuli. The continued presence of cardiac hypertrophy will ultimately develop into heart failure. The mitochondrion is the primary organelle of energy production, and its dysfunction plays a crucial role in the progressive development of heart failure from cardiac hypertrophy. Hispidulin, a natural flavonoid, has been substantiated to improve energy metabolism and inhibit oxidative stress. However, how hispidulin regulates cardiac ...[more]

PMID: 33324687

Similar Datasets

Project description:Purpose:RNA-Seq analysis was performed on mouse hearts with or without hispidulin treatment 4 weeks after arotic banding or sham surgery to determining the effect of hispidulin on pressure overload induced cardiac hypertrophy. Methods: the mRNA profiles of mouse hearts underwent sham or arotic banding surgery with treatment of hispidulin or DMSO were generated by RNA-seq analysis in triplicate. The expression level of gene was calculated by RSEM(v.1.2.12). Differential expression analysis was performed using the DESeq2(V 1.4.5). Results: RNA isolation, library construction, and sequencing were performed on a BGISEQ-500 (Beijing Genomic Institution, www.genomics.org.cn, BGI). For the gene expression analysis, the fold changes were also estimated according to the fragments per kilobase of exon per million fragments mapped (FPKM) in each sample. The significance of different gene expression was defined by the following filter criteria: false discovery rate (FDR) ≤0.001 and log2-ratio 1. After comparing of DMSO+AB group and hispidulin+AB group, we found that 113 genes were significantly differentially expressed. Gene ontology and cluster analysis indicated that alternated genes were enriched in fatty acid oxidation, glucose metabolism, TCA cycle, oxidative phosphorylation, hypertrophic cardiomyopathy, ECM organism, oxidative stress and unfolded protein binding. This result indicated that hispidulin improved mitochondrial function. Conclusions: Our study represents the first detailed analysis of heart transcriptomes, with biologic replicates, generated by RNA-seq technology. The optimized data analysis workflows reported here should provide a framework for comparative investigations of expression profiles. Our results show that NGS offers a comprehensive and more accurate quantitative and qualitative evaluation of mRNA content within a cell or tissue. We conclude that RNA-seq based transcriptome characterization would expedite genetic network analyses and permit the dissection of complex biologic functions.

Dataset Information

Hispidulin Attenuates Cardiac Hypertrophy by Improving Mitochondrial Dysfunction.

Publications

Hispidulin Attenuates Cardiac Hypertrophy by Improving Mitochondrial Dysfunction.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets